CAREER: Dissecting the Regulation of Ribosome Assembly by the Essential GTPase Bms1

The Scripps Research Institute, La Jolla CA

Investigators

Abstract

Intellectual Merit Protein molecules are important functional entities in all living cells. They are synthesized in a template-directed manner by ribosomes, large macro-molecular machines that themselves are composed of 78 proteins and 4 RNAs. As the synthesis of each protein depends on the ability of ribosomes to translate the genetic information encoded in its corresponding mRNA template, the accuracy of protein synthesis is in turn dependent on the correct assembly of ribosomes from their constituent protein and RNA components. One way by which correct ribosome synthesis is achieved is by ordering the assembly steps, so that a later step proceeds only after a prior step has been carried out accurately. The focus of this project is to elucidate the mechanism by which a regulatory protein called Bms1 regulates and orders essential steps in ribosome assembly, using the energy of GTP. These questions will be addressed experimentally using a combination of biochemical, kinetic and genetic approaches. Anticipated insights obtained from this work will have implications for other dynamic cellular assembly processes involving large RNA-protein complexes, including those participating in pre-mRNA splicing or in gene regulation involving small RNAs, known as RNA interference (RNAi). Broader Impact The education of young scientists requires two parallel tracks: Class-room teaching is intended to efficiently convey established knowledge to undergraduate and graduate students, while appropriately designed laboratory experiences introduce young scientists to the actual practice of science. Many of the PI?s graduate students and postdocs have expressed a strong interest in teaching careers, which makes it important to connect these two missions by raising excellent scientists that are also well-trained as teachers. Towards this goal, the PI has established in her first 18 months of funding an Introductory Laboratory in Biochemistry, which is now part of the core curriculum in the Biochemistry B.S. degree at the University of Michigan. Following the PI?s move to The Scripps Research Institute in Florida, she continues to build relationships with undergraduate students and other young scientists via two main thrusts that complement the Scripps graduate program. Scripps Florida has a strong community outreach program, whereby High School students and teachers join Scripps labs over the summer break to get a taste of science (in the case of students) or to have their skills and knowledge updated (in the case of high school teachers). The PI participates in this program. Furthermore, Scripps has a growing program to support excellent undergraduates (many from minority backgrounds) to conduct summer research internships with the end goal of promoting careers in science. The PI participates in this program by recruiting students and accepting them in her research group.